Synthetic peptides of the hamster beta 2-adrenoceptor as substrates
and inhibitors of the beta-adrenoceptor kinase
J. Benovic, J. Onorato, M. Lohse, H. Dohlman, C. Staniszewski, M. Caron, and R. Lefkowitz. Br J Clin Pharmacol, (1990)Benovic, J L Onorato, J Lohse, M J Dohlman, H G Staniszewski, C Caron,
M G Lefkowitz, R J England British journal of clinical pharmacology
Br J Clin Pharmacol. 1990;30 Suppl 1:3S-12S..
Abstract
1. The beta-adrenoceptor is one of a number of G protein-coupled receptors
which have been proposed to contain seven transmembrane alpha-helices.
The function of this receptor appears to be regulated by phosphorylation
by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides
which comprise each of the proposed intra- and extracellular domains
of the beta 2-adrenoceptor have been tested as potential substrates
and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which
encompass the middle and terminal portions of the carboxyl tail of
the receptor served as substrates by beta-adrenoceptor kinase. The
kinetics of the phosphorylation reaction, however, suggest that these
peptides are 10(6)-fold poorer substrate than the agonist occupied
receptor. 3. A number of synthetic peptides also served as inhibitors
of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase.
In particular, a peptide which comprised the first intracellular
loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most
effectively with an IC50 of 40 microM. 4. These results suggest that
multiple intracellular regions of the beta-receptor may serve as
potential sites of interaction with beta-adrenoceptor kinase. Moreover,
these regions may serve as potential targets for the development
of specific inhibitors of beta-adrenoceptor kinase which could be
used to block homologous desensitization.
Benovic, J L Onorato, J Lohse, M J Dohlman, H G Staniszewski, C Caron,
M G Lefkowitz, R J England British journal of clinical pharmacology
Br J Clin Pharmacol. 1990;30 Suppl 1:3S-12S.
%0 Journal Article
%1 Benovic1990
%A Benovic, J. L.
%A Onorato, J.
%A Lohse, M. J.
%A Dohlman, H. G.
%A Staniszewski, C.
%A Caron, M. G.
%A Lefkowitz, R. J.
%D 1990
%J Br J Clin Pharmacol
%K AMP-Dependent Acid Amino Animals Cricetinae Cyclic Data Electrophoresis, GTP-Binding Gel Inhibitors Kinase Kinases Kinases/isolation Kinetics Molecular Peptides/chemical Phosphorylation Polyacrylamide Protein Proteins/metabolism Receptor Sequence Specificity Substrate beta-Adrenergic beta/*chemistry/metabolism purification/*metabolism synthesis/*metabolism/pharmacology Adrenergic
%P 3S-12S
%T Synthetic peptides of the hamster beta 2-adrenoceptor as substrates
and inhibitors of the beta-adrenoceptor kinase
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2176526
%V 30 Suppl 1
%X 1. The beta-adrenoceptor is one of a number of G protein-coupled receptors
which have been proposed to contain seven transmembrane alpha-helices.
The function of this receptor appears to be regulated by phosphorylation
by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides
which comprise each of the proposed intra- and extracellular domains
of the beta 2-adrenoceptor have been tested as potential substrates
and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which
encompass the middle and terminal portions of the carboxyl tail of
the receptor served as substrates by beta-adrenoceptor kinase. The
kinetics of the phosphorylation reaction, however, suggest that these
peptides are 10(6)-fold poorer substrate than the agonist occupied
receptor. 3. A number of synthetic peptides also served as inhibitors
of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase.
In particular, a peptide which comprised the first intracellular
loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most
effectively with an IC50 of 40 microM. 4. These results suggest that
multiple intracellular regions of the beta-receptor may serve as
potential sites of interaction with beta-adrenoceptor kinase. Moreover,
these regions may serve as potential targets for the development
of specific inhibitors of beta-adrenoceptor kinase which could be
used to block homologous desensitization.
@article{Benovic1990,
abstract = {1. The beta-adrenoceptor is one of a number of G protein-coupled receptors
which have been proposed to contain seven transmembrane alpha-helices.
The function of this receptor appears to be regulated by phosphorylation
by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides
which comprise each of the proposed intra- and extracellular domains
of the beta 2-adrenoceptor have been tested as potential substrates
and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which
encompass the middle and terminal portions of the carboxyl tail of
the receptor served as substrates by beta-adrenoceptor kinase. The
kinetics of the phosphorylation reaction, however, suggest that these
peptides are 10(6)-fold poorer substrate than the agonist occupied
receptor. 3. A number of synthetic peptides also served as inhibitors
of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase.
In particular, a peptide which comprised the first intracellular
loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most
effectively with an IC50 of 40 microM. 4. These results suggest that
multiple intracellular regions of the beta-receptor may serve as
potential sites of interaction with beta-adrenoceptor kinase. Moreover,
these regions may serve as potential targets for the development
of specific inhibitors of beta-adrenoceptor kinase which could be
used to block homologous desensitization.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Benovic, J. L. and Onorato, J. and Lohse, M. J. and Dohlman, H. G. and Staniszewski, C. and Caron, M. G. and Lefkowitz, R. J.},
biburl = {https://www.bibsonomy.org/bibtex/26307f67bd8b6d837382583ac08525d4a/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {2ff36a9e47ab23ba0d1982e32cc97c69},
intrahash = {6307f67bd8b6d837382583ac08525d4a},
issn = {0306-5251 (Print) 0306-5251 (Linking)},
journal = {Br J Clin Pharmacol},
keywords = {AMP-Dependent Acid Amino Animals Cricetinae Cyclic Data Electrophoresis, GTP-Binding Gel Inhibitors Kinase Kinases Kinases/isolation Kinetics Molecular Peptides/chemical Phosphorylation Polyacrylamide Protein Proteins/metabolism Receptor Sequence Specificity Substrate beta-Adrenergic beta/*chemistry/metabolism purification/*metabolism synthesis/*metabolism/pharmacology Adrenergic},
note = {Benovic, J L Onorato, J Lohse, M J Dohlman, H G Staniszewski, C Caron,
M G Lefkowitz, R J England British journal of clinical pharmacology
Br J Clin Pharmacol. 1990;30 Suppl 1:3S-12S.},
pages = {3S-12S},
shorttitle = {Synthetic peptides of the hamster beta 2-adrenoceptor as substrates
and inhibitors of the beta-adrenoceptor kinase},
timestamp = {2010-12-14T18:22:38.000+0100},
title = {Synthetic peptides of the hamster beta 2-adrenoceptor as substrates
and inhibitors of the beta-adrenoceptor kinase},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2176526},
volume = {30 Suppl 1},
year = 1990
}